Purification of tumor-specific transplantation antigens (TSTA), the markers distinctive of neoplastic cells compared to their normal counterparts, may afford new reagents for active immunotherapy of hosts bearing supralethal neoplastic burdens. Preliminary studies have demonstrated the therapeutic effect of partially purified tumor extracts against recurrent neoplasms after incomplete tumor resection. This application seeks to extend these studies in a model relevant to human cancer: death from pulmonary metastases after adequate surgical resection. The experimental approach is unique because it is cognizant of the limited available source materials, employs non-cytolytic cell extraction techniques, and depends upon the use of tissue culture propagated rather than in vivo passaged neoplastic cells. The proposed studies will purify the TSTA of 3-methylcholanthrene-induced sarcomas from extracts obtained by 1% butanol, 3M KCl, or 0.2% octylglucoside treatment, and from spent tissue culture media. The active principle is fractionated from the crude extracts by preparative isoelectric focusing combined with high performance liquid chromatography. Antigenic activity is standardized by induction of immunoprotection, evocation of footpad swelling in sensitized hosts, and inhibition of a specific heterologous antibody. The antigens are tested for their capacity to enhance host resistance leading to destruction of pulmonary metastases and prolongation of host survival after adequate surgical resection by amputation of the tumor-bearing limb. Molecular engineering by immobilization of the partially purified materials or by incorporation into "cytomimetic" liposomes seeks to enhance immunogenicity by virtue of a more effective and prolonged stimulation of cytotoxic T cells. These investigations may provide a foundation for the development of therapeutic approaches, utilizing specific tumor anigen preparations, for the control of micrometastases in patients who have undergone adequate surgical resections, but are at high risk of recurrent disease.